The proposed research is divided into the two above separate areas. Objectives, Section A: The major objectives of the research are to 1) define the characteristics of the evolution of autoantibodies during the autoimmune response, 2) provide information which could establish that genetic control may exist which governs the formation of autoantibody and 3) clarify the stability of autoantibodies during autoimmune diseases. Objectives, Section B: The major objectives of this segment of the proposal are to a) define and study particular biophysical properties for and b) primary structural defects in monoclonal IgG cryglobulins which may clarify the means by which they self-associate and cryoprecipitate. Methods: The experimental methods for sectAon #1 will involve isolation of anti-IgG antibodies, preparation of anti-idiotypic antisera assays which determine relatedness of idiotypic determinants, and iso-electric focussing and primary amino-acid sequence analyses of light and heavy chains of these autoantibodies. Section #2 will involve utilization of circular dichroism and fluorescence spectroscopy, and techniques of analytical ultracentrifugation to determination and measure particular biophysical parameters of monoclonal IgG cryoblobulins, and primary amino acid sequence analysis of their heavy and light chains to define whether structural aberrations exist which may account for cryoprecipitation properties.